Nuñez-Sánchez María A, García-Villalba Rocío, Monedero-Saiz Tamara, García-Talavera Noelia V, Gómez-Sánchez María B, Sánchez-Álvarez Carmen, García-Albert Ana M, Rodríguez-Gil Francisco J, Ruiz-Marín Miguel, Pastor-Quirante Francisco A, Martínez-Díaz Francisco, Yáñez-Gascón María J, González-Sarrías Antonio, Tomás-Barberán Francisco A, Espín Juan C
Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, Campus de Espinardo, Murcia, Spain.
Mol Nutr Food Res. 2014 Jun;58(6):1199-211. doi: 10.1002/mnfr.201300931. Epub 2014 Feb 16.
Urolithins are bioactive metabolites produced by the gut microbiota from ellagitannins (ETs) and ellagic acid (EA). We investigated whether urolithins could be detected in colon tissues from colorectal cancer (CRC) patients after pomegranate extract (PE) intake.
CRC patients (n = 52) were divided into controls and PEs consumers (900 mg/day for 15 days) before surgical resection. PEs with low (PE-1) and high (PE-2) punicalagin:EA ratio were administered. Twenty-three metabolites, but no ellagitannins, were detected in urine, plasma, normal (NT) or malignant (MT) colon tissues using UPLC-ESI-QTOF-MS/MS (UPLC, ultra performance liquid chromatography; QTOF, quadrupole TOF). Free EA, five EA conjugates, gallic acid and 12 urolithin derivatives were found in colon tissues. Individual and total metabolites levels were higher in NT than in MT, independently of the PE consumed. The maximal mean concentration (1671 ± 367 ng/g) was found in NT after consumption of PE-1 and the lowest concentration (42.4 ± 10.2 ng/g) in MT with PE-2. Urolithin A or isourolithin A were the main urolithins produced (54 and 46% patients with urolithin A or isourolithin A phenotype, respectively). High punicalagin content (PE-2) hampered urolithins formation.
Significant levels of EA derivatives and urolithins are found in human colon tissues from CRC patients after consumption of pomegranate. Further studies are warranted to elucidate their biological activity.
尿石素是肠道微生物群从鞣花单宁（ETs）和鞣花酸（EA）产生的生物活性代谢产物。我们研究了在摄入石榴提取物（PE）后，能否在结直肠癌（CRC）患者的结肠组织中检测到尿石素。
CRC患者（n = 52）在手术切除前被分为对照组和PE消费者组（每天900毫克，共15天）。给予低（PE-1）和高（PE-2）石榴皮苷：EA比例的PE。使用超高效液相色谱-电喷雾四极杆飞行时间质谱联用仪（UPLC-ESI-QTOF-MS/MS，UPLC为超高效液相色谱，QTOF为四极杆飞行时间质谱）在尿液、血浆、正常（NT）或恶性（MT）结肠组织中检测到23种代谢产物，但未检测到鞣花单宁。在结肠组织中发现了游离EA、5种EA共轭物、没食子酸和12种尿石素衍生物。NT中单个和总代谢产物水平高于MT，与所摄入的PE无关。摄入PE-1后，NT中的最大平均浓度（1671±367纳克/克）被发现，而摄入PE-2的MT中的最低浓度（42.4±10.2纳克/克）。尿石素A或异尿石素A是主要产生的尿石素（分别有54%和46%的患者具有尿石素A或异尿石素A表型）。高石榴皮苷含量（PE-2）阻碍了尿石素的形成。
CRC患者在食用石榴后，其人类结肠组织中发现了显著水平的EA衍生物和尿石素。有必要进一步研究以阐明它们的生物活性。
